Nature-Inspired Alternatives to PEG for Next-Generation Long-Circulating Nanocarriers

Polyethylene glycol (PEG) has long been considered as the gold standard for imparting stealth properties to nanocarriers. However, the recent emergence of anti-PEG antibodies has spurred innovation toward nature-inspired alternatives. By mimicking the structural and functional architectures of biological systems such as cell membranes and protein corona, nanocarriers can be engineered to achieve prolonged circulation, superior biocompatibility, and active targeting capabilities. This perspective presents nature-inspired alternatives to PEG, including cell membranes and the protein corona, for extending the circulation time of nanocarriers. It also highlights current challenges associated with these nature-inspired alternatives and outlines future research directions to overcome these hurdles in designing next-generation long-circulating nanocarriers.